Polyol-Based Synthesis of Praseodymium Oxide Nanoparticles

Polyol Synthesis and Properties of AFe2O4 Nanoparticles …

It has become increasingly clear that the tumor-targeting properties of the nanoparticles optimized are not predictive of the performance. Farokhzad and Langer identified maximally targeted and maximally stealth surface engineering conditions for and performance using PSMA targeted aptamer-conjugated Dtxl-loaded self-assembled nanoparticles []. Nanoparticles were prepared with different compositions of the self-assembled diblock copolymers and aptamers, and the optimal aptamer density on the nanoparticle surface was initially determined . Increasing the ligand density to 5% significantly increased the nanoparticle uptake by the target cells (LNCaP), whereas further increase in aptamer density modestly increased the nanoparticle uptake. These results indicated that the optimum ligand density for PSMA-specific endocytosis was 10-80 nmol aptamer per μmol nanoparticle. LNCaP xenograft mouse models injected with the targeted nanoparticles showed that increasing the aptamer density from 0% to 5% significantly increased nanoparticle retention in tumors, but the retention decreased for aptamer densities beyond 10%. The authors suggested that higher aptamer densities may have reduced the nanoparticle stealth properties, resulting in rapid clearance by the liver. Gabizon . optimized the ligand density in the Her2-targeted PEGylated liposomal Dox system (HT-PLD) for ligand ratios of 7.5, 15, or 30 per liposome []. The best safety margin and performance resulted from a ligand density of 15 ligands per liposome in the HT-PLD formulation. A 30 ligand ratio accelerated plasma clearance in the tumor-bearing mice, and the 7.5 ligand ratio reduced cytotoxicity after passage.

Pyridyl disulfide linkers include cleavable disulfide bonds, which facilitates a quantitative evaluation of the reaction efficiency. Jon . calculated the concentration of surface-bound peptide molecules on the nanoparticles by quantifying the released pyridine-2-thione []. In an effort to develop integrin-targeted iron oxide nanoparticles as theranostic agents, amine-modified iron oxide nanoparticles were synthesized, and SPDP was added to convert the primary amine groups on the nanoparticles to sulfhydryl-reactive pyridyldisulfide groups. Conjugation between the thiol group-containing cyclic RGD peptides and the SPDP-activated nanoparticles produced pyridine-2-thione, which was immediately collected by spin filtering (at 100 K). The immobilized cRGD molecules were quantified based on the ultraviolet (UV) absorbance at 343 nm of the collected pyridine-2-thione filtrate, indicating that the average number of conjugated cRGD peptides on each nanoparticle was 0.39 wt%. This linker is useful for enhancing the intracellular gene silencing properties of siRNA. Bhatia . studied the gene-silencing efficacy of siRNA-conjugated QDs using cleavable (sulfo-LC-SPDP) or noncleavable (sulfo-SMCC) cross-linkers []. They immobilized thiol-modified siRNA specific for EGFP to amine-functionalized QDs via sulfo-LC-SPDP or sulfo-SMCC linkers and quantified the EGFP fluorescence intensity. The siRNA attached QDs via the sulfo-LC-SPDP linker provided greater silencing efficiency than those attached via the sulfo-SMCC linker. The cleavable disulfide cross-linker released siRNA from the nanoparticles into the intracellular reducing environment, which affected the interactions between the siRNA and the RNA induced silencing complex (RISC), which is necessary for gene knockdown.

Polyol synthesis of nanoparticles – …

Li . designed folate receptor-targeted hollow gold nanospheres carrying siRNA recognizing NF-B, a transcription factor related to the expression of genes involved in tumor development [,]. In this case, the photothermal effects of gold nanospheres were utilized to regulate drug release and as a therapeutic tool. Core/shell-structured hollow gold nanospheres (HAuNS, 40 nm) were initially synthesized, consisting of a thin gold wall with a hollow interior, and the structures displayed strong surface plasmon resonance (SPR) tunability in the near-IR region [-]. Thiol-modified siRNA duplexes directed toward the NF-B p65 subunit were then introduced to the surface of HAuNS. Folates were coupled to the nanoparticles through a thioctic acid-terminated PEG linker to produce F-PEG-HAuNS-siRNA (Figure A and B). Irradiation with a pulsed near-IR laser (800 nm) altered the absorption spectra of the HAuNS-siRNA solutions significantly, indicating a loss in the structural integrity and triggering the dissociation of siRNA from HAuNS, when demonstrated by TEM and fluorescence microscopy images. This mode of action is termed 'photothermal transfection'. Intravenous injection of the nanospheres into HeLa xenografts resulted in the distinct downregulation of the NF-B p65 subunit only for the folate-conjugated nanosphere treatment combined with near-IR laser irradiation, suggesting that selective targeting and endolysosomal escape of the nanoparticles was activated by near-IR irradiation at the tumor site. tests, in which therapy was combined with administration of irinotecan, a chemotherapeutic agent that increases sensitivity to NF-B inhibition, yielded a substantially enhanced apoptotic response (Figure C). micro-positron emission tomography (PET))/computed tomography (CT) imaging also confirmed the folate-mediated tumor-targeted theranostic properties of the nanostructures (Figure D). Although significant uptake of the nanoparticles was observed in the liver, spleen, kidney, and lung, no significant downregulation of p65 in these organs was observed as a result of the tumor-selective near-IR irradiation.

Polyol-Mediated Synthesis of Zinc Oxide Nanorods and ..

Wei and Gao used a single chain anti-prostate stem cell antigen (PSCA) antibody (scAbPSCA) as a specific 'address tag' for prostate cancer targeted imaging and therapy []. Prostate stem cell antigen is a prostate-specific glycosyl phosphatidylinositol-anchored glycoprotein that is marginally expressed in normal prostate and overexpressed in prostate cancer tissues []. As shown in Figure A, the scAbPSCA was prepared by cleaving intact AbPSCA with mercaptoethylamine (MEA), followed by linking to maleimide-PEG-carboxyl (MAL-PEG-COOH) and covalent conjugation to multifunctional polymeric vesicles that had been formed by the entrapping of superparamagnetic iron oxide (SPIO) nanoparticles and docetaxel (Dtxl) by amine-terminated poly(lactic-co-glycolic) acid. The scAbPSCA-Dtxl/SPIO-NPs were 147 nm in size, as determined by dynamic light scattering (DLS), and the amounts of SPIOs and Dtxl in the polymer matrix were 23 wt% and 6.02 wt%, respectively. The high drug encapsulation efficiency was due to partitioning of Dtxl into the oleic acid and oleylamine shell of the SPIOs, which acted as a drug reservoir, thereby exhibiting a triphasic drug release pattern rather than the common two-phase kinetic release pattern, including burst effects of an initial release stage, as observed in vesicles without SPIOs. An cytotoxicity study demonstrated the antiproliferative effects of the multifunctional vesicles toward prostate cancer cells. As indicated in Figures B and C, PC3 cells incubated with scAbPSCA-Dtxl/SPIO-NPs produced distinct darkened regions in the T2-weighted MRI compared to the polymeric vesicles without scAbPSCA or Endorem® (a commercial contrast, Guerbet, France). This result demonstrated that the scAbPSCA-Dtxl/SPIO-NPs could be used as MRI contrast agents for prostate-targeted imaging and real-time monitoring of therapeutic effects.

Synthesis of Au Nanoparticles in ..

AB - Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g-1). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM-1 s-1 and 185.58 mM-1 s-1 respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed.

of Cl − must be added to a polyol synthesis to provide ..

Medarova . synthesized a breast tumor-targeted nanodrug designed to specifically shuttle siRNA to human breast cancer while simultaneously allowing for the noninvasive monitoring of the siRNA delivery process []. The nanodrug consisted of SPIONs for MRI monitoring, Cy5.5 fluorescence dye for near-infrared (IR) optical imaging, and siRNA to target the tumor-specific antiapoptotic gene . Magnetic iron oxide nanoparticles are extensively used as multimodal imaging probes in combination with optical fluorescence dyes to obtain the benefits of optical imaging, such as rapid screening and high sensitivity. Because tumor-associated underglycosylated mucin-1 (uMUC-1) antigen is overexpressed in >90% of breast cancers and in >50% of all cancers in humans [], researchers have decorated nanodrugs with uMUC-1-targeting EPPT synthetic peptides for selective tumor targeting. As shown in Figure A, amine-functionalized superparamagnetic iron oxide nanoparticles with a cross-linked dextran coating (MN) have been prepared, and a Cy5.5 dye was conjugated to the surface of nanoparticles to produce MN-Cy5.5. Subsequently, thiol-modified, FITC-labeled EPPT peptides and siRNA were coupled to MN-Cy5.5 via a heterofunctional cross-linker, -succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The resulting therapeutic and diagnostic nanodrug (MN-EPPT-siBIRC5) exhibited superparamagnetic and fluorescence properties. After intravenous injection of the nanodrugs into mice with BT-20 breast tumors, the tumors were clearly imaged, as verified simultaneously by T2 MRI and near-IR optical imaging (Figure B). Systemic administration of the nanodrug once a week over 2 weeks induced considerable levels of necrosis and apoptosis in the tumors as a result of the siBIRC5-mediated inhibition of the antiapoptotic survivin protooncogene, translating into a significant decrease in tumor growth rate (Figure C). This tumor-targeted, imaging-capable nanodrug highlights the potential of MRI-guided tumor treatment, which can be used to quantify changes in the tumor volume over the treatment schedule as well as to guide selection of an optimal treatment time course.